PubMed | Neuro Rive Sud, University of New South Wales, Amiri Hospital, New York University and 9 more.
Type: Journal Article | Journal: Journal of neurology, neurosurgery, and psychiatry | Year: 2016
Discontinuation of injectable disease-modifying therapy (DMT) for multiple sclerosis (MS) after a long period of relapse freedom is frequently considered, but data on post-cessation disease course are lacking.(1) To compare time to first relapse and disability progression among DMT stoppers and propensity-score matched DMT stayers in the MSBase Registry; (2) To identify predictors of time to first relapse and disability progression in DMT stoppers.Inclusion criteria for DMT stoppers were: age 18years; no relapses for 5years at DMT discontinuation; follow-up for 3years after stopping DMT; not restarting DMT for 3months after discontinuation. DMT stayers were required to have no relapses for 5years at baseline, and were propensity-score matched to stoppers for age, sex, disability (Expanded Disability Status Score), disease duration and time on treatment. Relapse and disability progression events in matched stoppers and stayers were compared using a marginal Cox model. Predictors of first relapse and disability progression among DMT stoppers were investigated using a Cox proportional hazards model.Time to first relapse among 485 DMT stoppers and 854 stayers was similar (adjusted HR, aHR=1.07, 95% CI 0.84 to 1.37; p=0.584), while time to confirmed disability progression was significantly shorter among DMT stoppers than stayers (aHR=1.47, 95% CI 1.18 to 1.84, p=0.001). The difference in hazards of progression was due mainly to patients who had not experienced disability progression in the prebaseline treatment period.Patients with MS who discontinued injectable DMT after a long period of relapse freedom had a similar relapse rate as propensity score-matched patients who continued on DMT, but higher hazard for disability progression.
PubMed | University of California at San Francisco, Virginia Polytechnic Institute and State University, UOC Neurologia and Middle Tennessee State University
Type: | Journal: Brain informatics | Year: 2016
Theories of spreading activation primarily involve semantic memory networks. However, the existence of separate verbal and visuospatial memory networks suggests that spreading activation may also occur in visuospatial memory networks. The purpose of the present investigation was to explore this possibility. Specifically, this study sought to create and describe the design frequency corpus and to determine whether this measure of visuospatial spreading activation was related to right hemisphere functioning and spreading activation in verbal memory networks. We used word frequencies taken from the Controlled Oral Word Association Test and design frequencies taken from the Ruff Figural Fluency Test as measures of verbal and visuospatial spreading activation, respectively. Average word and design frequencies were then correlated with measures of left and right cerebral functioning. The results indicated that a significant relationship exists between performance on a test of right posterior functioning (Block Design) and design frequency. A significant negative relationship also exists between spreading activation in semantic memory networks and design frequency. Based on our findings, the hypotheses were supported. Further research will need to be conducted to examine whether spreading activation exists in visuospatial memory networks as well as the parameters that might modulate this spreading activation, such as the influence of neurotransmitters.
Pastorelli F.,Rizzoli Orthopaedic Institute |
Di Silvestre M.,Rizzoli Orthopaedic Institute |
Plasmati R.,Rizzoli Orthopaedic Institute |
Michelucci R.,UOC Neurologia |
And 9 more authors.
European Spine Journal | Year: 2011
Iatrogenic spinal cord injury is the most feared complication of scoliosis surgery. The importance of combined somatosensory evoked potentials (SEP) and motor evoked potentials (MEP) monitoring during spine surgery is well known. The current authors retrospectively evaluated the results of neurophysiological intraoperative monitoring (IOM) in a large population of patients who underwent surgical treatment for spinal deformity. Intraoperative monitoring of SEPs and transcranial electrical stimulation MEPs (TES-MEP) was performed in 172 successive patients who underwent surgical treatment of idiopathic (128 pts), congenital (15 pts) or syndromic (29 pts) scoliosis. The first 106 patients (Group 1) underwent only SEP monitoring, while the other 66 patients (Group 2) underwent combined SEP and TES-MEP monitoring, when the technique was introduced in the current authors' institution. Halogenate anaesthesia (Sevoflurane, MAC 0.6-1.2) was performed in Group 1 cases, total intravenous anaesthesia (Propofol infusion, 6-10 mg/kg/h) in Group 2 patients. A neurophysiological "alert" was defined as a reduction in amplitude (unilateral or bilateral) of at least 50% for SEPs and of 65% for TES-MEPs compared with baseline. In Group 1, two patients (1.9%) developed postoperative neurologic deficits following surgical correction of spinal deformity, consisting of permanent paraparesis in one case and transient paraparesis secondary to spinal cord ischaemia in the other. Twelve patients presented intraoperative significant changes of neurophysiological parameters that improved following corrective actions by surgeons and anaesthesiologists, and did not show any postoperative neurologic deficits. In ten cases the alert was apparently unrelated to surgical manoeuvres or to pharmacological interventions and no postoperative neurologic deficits were noted. Considering the patients of Group 2, two patients (3.0%) presented transient postoperative neurologic deficits preceded by significant intraoperative changes in SEPs and TES-MEPs. In five cases a transient reduction in the amplitudes of SEPs (1 patient) and/or TES-MEPs (5 patients) was recorded intraoperatively with no postoperative neurologic deficits. In conclusion, in the current series of 172 patients the overall prevalence of postoperative neurologic deficit was 2.3% (4 patients). When combined SEP and TES-MEP monitoring was performed, the sensitivity and specificity of IOM for sensory-motor impairment was 100 and 98%, respectively. Combined SEP and TES-MEP monitoring must be regarded as the neurophysiological standard for intraoperative detection of emerging spinal cord injury during corrective spinal deformity surgery. Early detection affords the surgical team an opportunity to perform rapid intervention to prevent injury progression or possibly to reverse impending neurologic sequelae. © 2011 Springer-Verlag.
Foster P.S.,Middle Tennessee State University |
Foster P.S.,University of Florida |
Drago V.,UOC Neurologia |
Mendez K.,Middle Tennessee State University |
And 3 more authors.
Journal of Clinical and Experimental Neuropsychology | Year: 2013
Some research has supported differences in mood functioning in patients with Parkinson's disease (PD) whose motor symptoms begin at the left or right hemibody. Also, a relationship between disease duration and mood disturbances has been reported, but only for PD patients with right hemibody onset. There have been no investigations reported examining the potential interactions between side of onset of motor symptoms, mood, and disease duration on cognitive functioning. Hence, the purpose of this investigation was to determine whether the interaction between mood and disease duration differentially affects cognitive functioning in patients with PD whose motor symptoms begin at the left and right hemibody. A total of 33 PD patients with left hemibody onset and 29 PD patients with right hemibody onset were given a battery of tests to evaluate mood functioning and general cognitive functioning. As predicted, the results indicated that the interaction of disease duration and mood significantly predicted cognitive functioning for PD patients with right hemibody onset of symptoms but not for PD patients with left hemibody onset of symptoms. Interestingly, an unexpected finding was a significant positive relationship between disease duration and energy level for patients with left hemibody onset but not for patients with right hemibody onset. These results indicate that mood problems and disease duration interact to significantly affect cognitive functioning but only for those PD patients who experience a right hemibody onset of symptoms. © 2013 Copyright Taylor and Francis Group, LLC.
Tavian D.,Catholic University of the Sacred Heart |
Missaglia S.,Catholic University of the Sacred Heart |
Redaelli C.,Catholic University of the Sacred Heart |
Pennisi E.M.,UOC Neurologia |
And 5 more authors.
Human Molecular Genetics | Year: 2012
The lack of adipose triglyceride lipase (ATGL), a patatin-like phospholipase domain-containing enzyme that hydrolyzes fatty acids from triacylglycerol (TAG) stored in multiple tissues, causes the autosomal recessive disorder neutral lipid storage disease with myopathy (NLSD-M). In two families of Lebanese and Italian origin presenting with NLSD-M, we identified two new missense mutations in highly conserved regions of ATGL (p.Arg221Pro and p.Asn172Lys) and a novel nonsense mutation (p.Trp8X). The Lebanese patients harbor homozygous p.Arg221Pro, whereas the Italian patients are heterozygotes for p.Asn172Lys and the p.Trp8X mutation. The p.Trp8X mutation results in a complete absence of ATGL protein, while the p.Arg221Pro and p.Asn172Lys mutations result in proteins with minimal lipolytic activity. Although these mutations did not affect putative catalytic residues or the lipid droplet (LD)-binding domain of ATGL, cytosolic LDs accumulated in cultured skin fibroblasts from the patients. The missense mutations might destabilize a random coil (p.Asn172Lys) or a helix (p.Arg221Pro) structure within or proximal to the patatin domain of the lipase, thereby interfering with the enzyme activity, while leaving intact the residues required to localize the protein to LDs. Overexpressing wild-type ATGL in one patient's fibroblasts corrected the metabolic defect and effectively reduced the number and area of cellular LDs. Despite the poor lipase activity in vitro, the Lebanese siblings have a mild myopathy and not clinically evident myocardial dysfunction. The patients of Italian origin show a late-onset and slowly progressive skeletal myopathy. These findings suggest that a small amount of correctly localized lipase activity preserves cardiac function in NLSD-M. © The Author 2012. Published by Oxford University Press. All rights reserved.
Alessandro S.,IRCCS Fondazione S. Lucia |
Alessandro S.,NeuroLogica |
Ceravolo R.,University of Pisa |
Brusa L.,U.O.C. Neurologia |
And 8 more authors.
Journal of the Neurological Sciences | Year: 2010
Between 2005 and 2007, six patients affected by idiopathic Parkinson's disease (IPD) were submitted to the bilateral implantation (and subsequent deep brain stimulation - DBS) of the pedunculopontine nucleus (PPN) plus the subthalamic nucleus (STN). This review synthesizes the effects of PPN low-frequency stimulation on non-motor functions, focusing on patient sleep quality and cognitive performance. If not associated to STN-DBS, PPN-DBS promoted a modest amelioration of patient motor performance. However, during PPN-DBS, they experienced on the one hand a significant improvement in executive functions and working memory, on the other hand a beneficial change in sleep architecture. Overall, the limited sample hampers definite conclusions. Yet, although the PPN-DBS induced motor effects are quite disappointing (discouraging extended trials based upon the sole PPN implantation), the neuropsychological profile supports the contention by which in selected PD patients, with subtle cognitive deficits or vanished efficacy of previous implanted STN, PPN-DBS might still represent a reliable and compassionate option. © 2009 Elsevier B.V. All rights reserved.
Stefani A.,University of Rome Tor Vergata |
Brusa L.,UOC Neurologia |
Olivola E.,University of Rome Tor Vergata |
Pierantozzi M.,University of Rome Tor Vergata |
Martorana A.,University of Rome Tor Vergata
Journal of Neural Transmission | Year: 2012
Dementia has become a relevant problem associated with the elderly in our countries. Increased interest in the field has yielded a copious literature, so far mostly centered on Alzheimer's dementia. Cerebrospinal fluid (CSF) analysis combined with neuropsychology, even in absence of neuroimaging, represents the gold standard to reach a diagnosis when cortical cognitive impairment prevails. In view of this, low levels of CSF amyloid peptides β (Aβ) and high tau/Aβ protein ratio, despite prominent impairment of executive functions or concomitant vascular burden, facilitate the diagnosis of Alzheimer's disease. Conversely, an early cognitive impairment occurring in patients suffering from Parkinson's disease (PD) or Lewy body disorders (LBDs), both diagnoses posed on pure clinical grounds, remains quite elusive in term of biomarkers or neuropsychological assessment. Whether PD with dementia (PDD) and dementia with Lewy bodies (DLB) represent further steps along with a continuum of the same progressive degeneration due to Lewy bodies deposition, rather then the association of Lewy bodies and Aβ pathology, remains a challenging issue. Aim of this work is to set a state-of-the-art on the neuropsychological profiles of both or DLB. Then, we will focus on the ongoing controversies about the specificity of the standard CSF biomarkers if applied to extrapyramidal disorders. Our conclusions are that the CSF pattern, in PDD and DLB, can certainly be distinct from that in AD, though mechanisms leading to dementia could be shared among them. It is possible that, by combining imaging tracers, neuropsychologically careful assessment and renewed CSF biomarkers, DLB can be better distinguished in subgroups, depending on the presence or absence of a relevant amyloid burden. However, more complete data, possibly collected in fieri during the progressive derangement of cognitive abilities, are needed to improve our ability to decipher and treat these entities. © Springer-Verlag 2012.
Calza L.,University of Bologna |
Beltrami D.,University of Bologna |
Gagliardi G.,University of Bologna |
Ghidoni E.,UOC Neurologia |
And 3 more authors.
Maturitas | Year: 2015
Due to increased life expectancy, the prevalence of cognitive decline related to neurodegenerative diseases and to non-neurological conditions is increasing in western countries. As with other diseases, the burden might be reduced through personalized interventions delivered at early stages of the disease. Thus, there is an increasing demand, from both social and healthcare systems, for instruments and strategies to recognize cognitive decline, and possibly distinguish the precursor of serious neurodegeneration from "benign senile forgetfulness" or the temporary consequences of illness or trauma. However, this goal faces both technical and ethical issues. In this article we deal with the following: (i) re-definition of cognitive decline and its relationship with frailty definitions, starting from the recent work of international consensus groups for presymptomatic Alzheimer disease recognition; (ii) ethical problems concerning anonymous and personalized cognitive screening and the need for appropriate counselling; (iii) the need for more sensitive and specific tools to detect and distinguish pathological levels of cognitive decline and delineate the contribution of non-pathological decline to accumulated frailty impacts and (iv) the potential of the language domain and spontaneous speech analyses. © 2015 Published by Elsevier Ireland Ltd.
Ceravolo R.,University of Pisa |
Brusa L.,U.O.C. Neurologia |
Galati S.,University of Rome Tor Vergata |
Volterrani D.,University of Pisa |
And 7 more authors.
European Journal of Neurology | Year: 2011
Background and purpose: To evaluate the effects of 25-Hz deep brain stimulation of the nucleus tegmenti pedunculopontini (PPTg) on brain metabolic activity. Methods: Six patients with Parkinson's disease (PD) who had bilateral stereotactic implantation of PPTg at least 12months prior to evaluation were included in our study. All underwent, in separate sessions, 18-FDG-PET in core assessment programme for intra-cerebral transplantation as well as motor evaluation [Unified Parkinson's disease rating scale (UPDRS) - section III] and a battery of cognitive testing. Results: PPTg-ON (low bipolar contacts, 25Hz) promoted a significant increase of glucose utilization in bilateral prefrontal areas including dorsolateral prefrontal cortex (DLPFC, BA9), orbito-frontal cortex (BA47), anterior cingulate (BA 25-32), superior frontal gyrus (BA 10) and supramarginal gyrus (BA40); a significant increase of uptake and consumption of FDG also occurred in the left ventral striatum, left subgyral (BA 46), right insula (BA 13) and right superior temporal gyrus (BA 22). PPTg-ON was associated with a significant decrease of glucose utilization in the left cerebellar anterior lobe (culmen) and right cerebellar posterior lobe (declive). In the same patients, PPTg-ON improved delayed recall (P<0.05) and executive functions whilst the UPDRS revealed a modest (-21%) and variable treatment effect. Conclusions: Low frequency stimulation of PPTg, a sub-region of the pedunculopontine nucleus complex, causes a minor motor benefit but a peculiar profile of cognitive improvement associated with a significant increase in FDG consumption in both prefrontal areas and mono-lateral ventral striatum. These data are consistent with multiple limbic and/or associative domains modulated by PPTg stimulation in our patients with PD. © 2010 The Author(s). European Journal of Neurology © 2010 EFNS.
Poletti M.,UOC Neurologia
Rivista di Psichiatria | Year: 2010
Reward processing permits to establish if and how an environmental stimulus or a future goal is reinforcing or punishing for the subject. This process is at the basis of reinforcement learning and decision making; is principally based on the orbitofrontal cortex and its connections with the striatum and the limbic system. If a dysfunctional reward processing has been often reported in substance abusers or pathologic gamblers, recent studies reported a dysfunction of this process in patients with other psychiatric disorders, previously not assessed by this experimental perspective, for example attention deficit/hyperactivity disorder, mood disorders, eating behaviour disorders and cluster B personality disorders. Experimental findings on a dysfunctional reward processing in these disorders are reviewed and discussed, in order to trace directions for future studies, that need to clarify if different dysfunctions are associated to different psychiatric disorders.